When to administer intravenous (IV) iron to patients with heart failure?

From the Guidelines

Intravenous (IV) iron should be given to heart failure patients with iron deficiency, defined as ferritin <100 μg/L or ferritin 100-299 μg/L with transferrin saturation <20%, as it improves functional capacity, quality of life, and reduces heart failure hospitalizations. This treatment is particularly beneficial for patients with symptomatic heart failure with reduced ejection fraction (HFrEF), regardless of anemia status, as shown in studies such as FAIR-HF and CONFIRM-HF 1. Common IV iron preparations include iron carboxymaltose (500-1000 mg per dose), iron sucrose (200-300 mg per dose), and ferric derisomaltose (1000 mg per dose), typically administered over 15-60 minutes depending on the preparation. Initial dosing is based on body weight and hemoglobin levels, with maintenance doses given as needed based on follow-up iron studies every 3-6 months, as recommended in guidelines such as the 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 1 and the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1. Key points to consider when administering IV iron include:

• Ruling out active infection and assessing for allergic risk, as rare hypersensitivity reactions can occur
• Monitoring for improvements in functional capacity, quality of life, and reductions in heart failure hospitalizations
• Considering the use of IV iron in patients with symptomatic HFrEF and iron deficiency, as recommended by guidelines such as the 2018 European Journal of Heart Failure article on screening, diagnosis and treatment of iron deficiency in chronic heart failure 1. Oral iron is generally ineffective in heart failure patients due to poor absorption related to hepcidin dysregulation and gastrointestinal edema, making IV iron a preferred treatment option 1.

From the FDA Drug Label

2 DOSAGE AND ADMINISTRATION

1. 1 Recommended Dosage Recommended Dosage in Patients with Iron Deficiency with Heart Failure See Table 1 for recommended dosage for treatment of iron deficiency in patients with heart failure and New York Heart Association class II/III to improve exercise capacity Table 1: Recommended Dosage in Patients with Iron Deficiency with Heart Failure Weight less than 70 kg Weight 70 kg or more Hb (g/dL) Hb (g/dL) < 10 < 10 10 to 14 10 to 14

   14 to < 15 > 14 to < 15 Day 1 1,000 mg 1,000 mg 500 mg 1,000 mg 1,000 mg 500 mg Week 6 500 mg No dose No dose 1,000 mg 500 mg No dose Administer a maintenance dose of 500 mg at 12,24 and 36 weeks if serum ferritin <100 ng/mL or serum ferritin 100-300 ng/mL with transferrin saturation <20%.

Heart failure patients with iron deficiency should be given IV iron according to the recommended dosage in Table 1, which is based on the patient's weight and hemoglobin (Hb) level.

• For patients weighing less than 70 kg with Hb < 10 g/dL, the recommended dose is 1,000 mg on Day 1 and 500 mg on Week 6.
• For patients weighing 70 kg or more with Hb < 10 g/dL, the recommended dose is 1,000 mg on Day 1 and 1,000 mg on Week 6 if Hb is 10-14 g/dL, or 500 mg on Week 6 if Hb is > 14 to < 15 g/dL. A maintenance dose of 500 mg may be administered at 12,24, and 36 weeks if certain conditions are met, such as serum ferritin < 100 ng/mL or serum ferritin 100-300 ng/mL with transferrin saturation < 20% 2.

From the Research

Indications for IV Iron in Heart Failure Patients

• IV iron therapy is recommended for patients with heart failure and reduced or mildly reduced left ventricular ejection fraction who have iron deficiency 3, 4, 5, 6, 7
• Iron deficiency is common in heart failure patients and is associated with more severe symptoms, worse quality of life, and an increased risk of hospitalizations and death 3, 7

Definition of Iron Deficiency in Heart Failure

• The current definition of iron deficiency in heart failure has serious flaws, and a serum ferritin <100 µg/L does not identify patients more likely to respond to intravenous iron 3
• A more evidence-based definition of iron deficiency is the presence of hypoferremia, as reflected by a transferrin saturation (TSAT) <20% 6
• Patients with TSAT <20% are more likely to have a beneficial response to intravenous iron 3, 6

Benefits of IV Iron Therapy in Heart Failure

• IV iron therapy has been shown to improve patient well-being, reduce the risk of hospitalizations, and improve functional capacity and quality of life in heart failure patients with iron deficiency 4, 5, 7
• IV iron therapy may also be associated with a reduction in the risk of hospitalizations for worsening heart failure 4

Timing of IV Iron Administration

• There is no specific guidance on the exact timing of IV iron administration in heart failure patients, but it is recommended to consider IV iron therapy in patients with heart failure and reduced ejection fraction and iron deficiency (serum ferritin <100 μg/L, or ferritin between 100 and 299 μg/L with TSAT <20%) to provide symptomatic relief and improve exercise capacity and quality of life 5